In spite of comprehensive prenatal care, complex neonatal intensive care units, expensive monitoring devices and the liberal use of potent antibiotics, bacterial infection in the human neonate remains common and the resulting morbidity and mortality exceedingly high. Numerous studies have defined abnormalities in the neonate's host defense mechanism. These include defects in antibody production, complement component levels and function and lymphocyte responses to specific antigens. In addition, numerous reports have appeared on the matabolic and microbicidal activity of neonatal phagocytes. In each case, however, the abnormalties have not been profound and their functional significance in the neonate open to some question. Several investigators including ourselves have also reported that granulocytes from neonates have defective chemotactic responses. In contrast to the other mentioned abnormalities, the defect in cell movement is constant and profound in nature (5% to a high of 27% of adult values). Furthermore, human neonates commonly suffer from bacterial and fungal infectins that are often associated with impared inflammatory responses (cutaneous abscesses, cellulitis, pneumonia, mucocutaneous candidiasis). Although a number of investigators have reported the presence of the defect, almost no studies on the mechanisms of the abnormality have appeared in the literature. We proposed to investigate the cellular mechanisms involved in the chemotactic response in neonatal PMNs and compare this to those of adult PMNs. The processes to be examined include changes in call surface charge, calcium flux, Na+ flux, cyclic nucleotide generation, microtubular and microfilament function. In addition we will examine cell surface receptors and receptor metabolism and migration. Lastly, an attempt will be made to determine if autooxidative membrane damage could contribute to the abnormality in cell movement observed. Hopefully, a clear definition of the mechanism involved in defective neonatal granulocyte movement will lead to a better understanding of evolving cellular function in the human neonate and the development of pharmacologic regimens for preventing or attenuating such abnormalities.